Method and apparatus for diagnosis of coronary artery disease

ABSTRACT

Method and apparatus for recurrently obtaining a measure of the systolic slope of the blood pressure wave in a subject&#39;s artery during a range of physical activity, or exercise, are disclosed. A plot, or record, of the slope measurements versus heart beat rate, point in an exercise protocol, or the like, is provided from which subjects having coronary artery disease (CAD) may be distinguished from subjects without CAD.

RELATED APPLICATION

This is a divisional of co-pending application Ser. No. 272,542 filed onJune 11, 1981, now U.S. Pat. No. 4,649,929.

BACKGROUND OF THE INVENTION

Numerous means for obtaining blood pressure measurements are knownincluding both invasive and noninvasive means. A number of noninvasivemeasuring means are disclosed in an article by C. S. Weaver, J. S.Eckerley, P. M. Neugard, C. T. Warnke, J. B. Angell, S. C. Terry and J.Robinson, entitled "A Study of Non-invasive Blood Pressure MeasurementTechniques" presented at a conference held at Stanford University inSeptember, 1978 and published by the Society of Photo-OpticalInstrumentation Engineers.

The use of pulse rate and rhythm measurements as well as measurements ofsystolic and diastolic blood pressure in the diagnosis of cardiovasculardisease has long been known. Electrocardiograph (ECG) measurements alsoare of well known diagnostic significance in heart disease.

SUMMARY OF THE INVENTION AND OBJECTS

An object of the present invention is the provision of improveddiagnostic method and apparatus for the improved diagnosis of coronaryartery disease.

An object of the present invention is the provision of improveddiagnostic method and apparatus of the above-mentioned type whichprovides a measure of heart contractility of a subject during a range ofexercise.

The above and other objects and advantages of this invention areobtained by recurrently obtaining a measure of the time rate of changein the intra-arterial pressure of a subject during systole (i.e.systolic slope of blood pressure waves in an artery of a subject)before, during and after exercise performed by the subject. Actualvalues of these measurements at different times in the exerciseprotocol, as well as certain changes therein during the exerciseprotocol are determined and compared to corresponding measurementsobtained from persons without known CAD for diagnosis of CAD in thesubject.

One means for obtaining recurrent measures of the systolic slope of thearterial blood pressure waves includes the use of an inflatable cuffwhich is inflatable to a pressure above systolic pressure and deflatableto a pressure below diastolic pressure. A pressure transducer isconnected to the inflatable cuff for generating a signal which is afunction of cuff pressure. A microphone detects Korotkov sounds duringdeflation of the cuff, and electrodes attached to the subject pick-upelectrocardiograph signals. A K-sound detector detects Korotkov soundsfrom the microphone and an R-wave peak detector detects the peak of theECG R-wave. The K-sound and R-wave signals from the detectors areconverted to signals for use by a computer, and the pressure transduceroutput is converted to digital form for transfer to the computer andstorage in the computer memory. The R-wave and K-sound signals may besupplied as interrupt signals to the computer, with the time of arrivalof such signals being stored in the computer memory. Alternatively, ECGand/or Korotkov sound waveforms may be digitized and input to softwareR-wave and/or K-sound detectors in the computer with the time of arrivalof the software detected R-waves and/or K-sounds being stored in thecomputer memory. The time intervals between the time of arrival of theR-wave signals and the associated K-sound signals during a cuffdeflation are determined by the computer and the resultant RK intervalsand associated cuff pressures are stored in the computer memory. The RKintervals are processed to discriminate between true Korotkov sounds andartifacts. Using minimum mean-squared fitting techniques, a straightline is fitted by the computer to the collection of true RK intervalversus cuff pressure points, which line has a slope inverselyproportional to the systolic slope of the arterial blood pressure wave.During a range of exercise a plurality of such "RK-slope" measurementsare obtained. These measurements, and changes therein, obtained duringan exercise protocol are compared to corresponding measurements andchanges therein obtained from healthy subjects for the diagnosis ofcoronary artery disease (CAD) in the subject.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be better understood from the following descriptionwhen considered with the accompanying drawings. In the drawings, whereinlike reference characters refer to the same parts in the several views:

FIG. 1 is a plot of an electrocardiographic signal and an associatedarterial blood pressure wave showing RK intervals; measurements of whichare made using the system shown in FIG. 3;

FIGS. 2A and 2B each show graphical representations of arterial bloodpressure waves at different times during a range of exercise forsubjects without and with, respectively, coronary artery disease;

FIG. 3 is a simplified block diagram of a system for recurrentlyobtaining a measure of the systolic slope of a blood pressure wave andfor displaying said measurements, which system embodies the presentinvention;

FIG. 4 is a plot of RK interval as a function of cuff pressure for usein explaining the operation of the system shown in FIG. 3;

FIGS. 5A-5D are graphs of measurements of slope versus heartbeat ratefor subjects with no known coronary artery disease;

FIGS. 6A-6D are graphs which are similar to those shown in FIGS. 5A-5Dfor subjects known to have coronary artery disease;

FIG. 7 is a flow chart for use in explaining operation of the systemshown in FIG. 3;

FIG. 8 shows graphs of measurements of "RK-slope" versus time for asubject with and a subject without coronary artery disease; and

FIG. 9 shows details of a step of the flow chart of FIG. 7 whereinvarious parameters of the systolic slope measurements are employed bythe computer for use in identifying subjects with CAD.

Reference first is made to FIG. 1 wherein portions of anelectrocardiograph signal 10 and associated brachial artery pressurewave 12 are shown. In accordance with the present invention, recurrentmeasurements of the systolic slope of the pressure wave are made duringan exercise routine. Measurements of the slope together withmeasurements of certain changes therein which occur during the course ofan exercise protocol are evaluated based on corresponding measurementsobtained from other subjects with and without known coronary arterydisease (CAD) for diagnosis of the disease. Various methods forobtaining a measure of the systolic slope are known in the art,including those described in the abovementioned Weaver et al article.Apparatus of this invention which makes use of one of theslope-measuring methods disclosed in the article is shown in FIG. 3 anddescribed below. First, however, systolic slopes of subjects without CADand subjects with CAD shown in FIGS. 2A and 2B, respectively, will bedescribed, together with some differences therein useful in thediagnosis of CAD. The systolic slopes depicted in FIG. 2B arerepresentative of many, but not all, types of CAD, and are shown forpurposes of illustration only.

Systolic slope portions of pressure waves obtained before, during andafter exercise stress are depicted in FIGS. 2A and 2B. For purposes ofdescription, the same reference characters are used in FIGS. 2A and 2Bfor pressure pulses obtained at the same relative time during anexercise protocol, except for the use of the suffixes A and B in FIGS.2A and 2B, respectively. The at rest, before exercise, waves areidentified by reference characters 20A and 20B. Both of these waves showsystolic and diastolic pressures which are considered to be withinnormal ranges thereof. The systolic slope of the waves, however, differ,with the systolic slope of pressure wave 20A being greater than that ofpressure wave 20B. Typically, the pre-exercise, resting, systolic slopefor subjects with CAD is less than that of subjects without CAD.

Pressure waves 22A-1, 22A-2 and 22A-3 shown in FIG. 2A are typical ofthose observed after 2, 4 and 6 minutes, respectively, of exercise. Forthe subject without CAD, it will be seen that the systolic slope slowlyincreases with increasing exercise. Although not seen in FIG. 2A, withincreasing exercise the systolic slope generally increases to a maximumvalue, and remains substantially at said value during continuedexercise.

As seen in FIG. 2B, representative pressure waves 24B-1, 24B-2 and 24B-3during exercise for a subject with CAD show an increase in the systolicslope with exercise, followed by a decrease therein with furtherexercise. When the left ventricle contracts, not all of the blood isejected therefrom. Typically, when a subject is at rest, only 50 percentis ejected. The ejection percentage, divided by 100, is the ejectionfraction (EF). EF can be measured by injecting a radioactive solutioninto the blood and then "photographing" the left ventricle with aradionuclide camera at a rate of approximately 30 to 40 photographs persecond. These photographs allow the size of the left ventricle to bedetermined at a number of points during a heart beat, from whichdeterminations of EF can be calculated. Except for a dangerous techniquewhereby an X-ray dye is injected directly into the coronary arteries, EFmeasurements during exercise heretofore have provided the most accurateknown indicators of CAD. Typically, a healthy subject's EF willgradually increase during exercise, while that of a subject with CAD,first will increase, and then decreases. It is commonly believed thatthis decrease is due to a decrease in heart contractility. A lower heartcontractility lowers the systolic slope of the pressure pulse in thebrachial artery. Simultaneous radio-isotope EF and systolic slopemeasurements have been made on subjects with and without CAD and theabove-described correlation between the EF and slope measurements hasbeen observed.

After exercise other differences in the changing systolic slope patternsbetween healthy subjects and subjects with CAD often are observed, andare illustrated in FIGS. 2A and 2B. Pressure waves 24A-1, 24A-2 and24A-3 are typical of a healthy subject observed 2, 4 and 6 minutes,respectively, after exercise. Immediately following exercise, thesystolic slope remains substantially the same as the slope immediatelybefore the end of exercise, and then slowly decreases with time to thepre-exercise, resting slope. This pattern is in contrast to thatobserved in many subjects with CAD wherein, after exercise, the systolicslope often decreases beneath the pre-exercise, resting, slope beforereturning to such pre-exercise slope. Pressure wave 24B-3 in FIG. 2B, at6 minutes after exercise, is seen to have a systolic slope less thanthat of the pre-exercise wave 20B. As noted above, such a low systolicslope correlates with low heart contractility and low EF and representsan immediate dangerous physical condition. It here will be noted thatalthough measurements are obtained at corresponding times in theexercise routines for FIGS. 2A and 2B, different effort may be expendedby the subjects during the exercise portion of the routines. In FIGS.5A-5D and 6A-6D plots of measurements of systolic slope as a function ofheart beat rate are shown which provide the physician with an indicationof the amount of effort exerted by each subject during the exerciseroutine.

As noted above, various means are known for measuring blood pressure,and the time-derivative of pressure during the systolic slope whichprovides a measure of the slope. Apparatus for obtaining a measure ofthe systolic slope of the blood pressure wave embodying the presentinvention is shown in FIG. 3, to which reference now is made. Theillustrated apparatus includes an inflatable cuff 30 for encircling asubject's limb, such as upper arm, and a pressure source 32 connected tothe cuff through a pressure controller 34. Cuff pressure is sensed by apressure transducer 36, the analog output from which is connectedthrough an amplifier 38 to the input of an analog to digital converter40 for conversion to digital signal form. The digitized cuff pressuresignal is connected through a digital multiplexer 42 to a computer 44which includes memory 44A where cuff pressure signals obtained during acuff deflation temporarily are stored for use in computing a measure ofthe systolic slope of blood pressure waves during said deflation.

With the cuff 30 attached to the upper arm of the subject, the cuff isinflated to a pressure above systolic pressure. Then, as the cuffpressure is decreased, the first Korotkov sound appears at the systolicpressure, and the last at the diastolic pressure. A microphone 46 picksup the Korotkov sound (K-sound) at a plurality of cuff pressures betweensystolic and diastolic. The microphone output signal is amplified byamplifier 48, and the amplifier output is supplied both to a signalconverter 50 and to a K-sound detector 52. The converter 50 simply mayinclude a oneshot for generation of a pulse output in response to anamplified K-sound output from amplifier 48, which pulse output isconnected to the multiplexer 42. The K-sound detector 52 distinguishesbetween true K-sounds and artifacts, and produces an output in responseto said true K-sounds, which output is connected to an address input ofthe multiplexer. In the presence of an output from the K-sound detector,the output from the converter 50 is connected through the multiplexer 42to an interrupt input of the computer 44 to produce a K-sound timingsignal which, together with an associated R-wave timing signal, providesa measure of the RK interval.

ECG electrodes 60 attached to the subject's body pick up ECG signalswhich are amplified by amplifier 62 and then supplied to a converter 64and to an R-peak detector 66. As with converter 50, the converter 64also may include a one-shot for generation of a pulse output in responseto the R-wave component of the amplified ECG signal. The pulse outputfrom the converter 64 is connected to the multiplexer 42 for connectionas an interrupt input to the computer 44. The R-peak detector detectsthe R-wave of the ECG signal while discriminating against noise andother components, such as the P and T wave components. The R-peakdetector output is supplied as an address input to the multiplexer 42for connection of the output from the converter 64 to an interrupt inputof the computer 44 when an R wave is detected. The difference in timebetween the arrival of an R wave input and associated K-sound signal atthe interrupt inputs to the computer provides a measure of the RKinterval, which interval is temporarily stored in the computer memory44A for use with other such RK interval values obtained at differentcuff pressures for use in calculating a value related to the systolicslope of the subject's arterial blood pressure wave.

Another address input for the multiplexer 42 is obtained from thecomputer 44 through a control unit 70. Under control of unit 70, themultiplexer 42 is switched for connection of cuff pressure signals fromthe A/D converter 40 to the computer 44. Also, multiplexer address inputinformation is supplied to the computer 44 through the control unit 70for use by the computer in controlling operation of the multiplexer. Akeyboard 72 may be included for manual supply of information to thecomputer, such as the name of the subject to be tested, facts concerningthe subject, and various points in the exercise protocol including thestart and end of the exercise portion thereof. Data display andrecording unit 74 may be used to display and/or record systolic slopeinformation at different exercise levels of the subject. As will becomeapparent, using the RK interval and cuff pressure information, thecomputer may be programmed to compute systolic and diastolic bloodpressure, which values also may be displayed and/or recorded by unit 74.A system of the type shown in FIG. 3 for measuring systolic anddiastolic blood pressure is shown in the above-mentioned Weaver et alarticle entitled A Study of Non-invasive Blood Pressure MeasurementTechniques, the entire disclosure of which article specifically isincorporated by reference herein. However, the relationship betweensystolic slope as a function of exercise stress and CAD is not disclosedin the article, nor are means for the diagnosis of CAD usingmeasurements of the systolic slope, and changes in the slope, disclosedtherein.

Reference again is briefly made to FIG. 1 wherein the relationshipbetween systolic slope of the blood pressure wave 12 and RK interval isshown. The RK interval, i.e. the time interval between the occurrence ofthe R wave peak and the associated K-sound, is maximum at systolicpressure and minimum at diastolic pressure. As the cuff pressure isdecreased from systolic, the RK interval also decreases. As is wellunderstood, the K-sounds are of maximum amplitude intermediate the upperand lower ends of the systolic slope and gradually decrease to zero tosystole and diastole.

During cuff deflation, a plurality of RK interval measurements areobtained, and a plot of such measurements as a function of cuff pressureis shown in FIG. 4 to which reference now is made. There, a straightline 80 is shown fitted through the series of points using minimummean-squared error fitting techniques readily implemented by use of thecomputer. The slope, ΔRK- interval/Δ pressure, of the line is inverselyproportional to the systolic slope of the blood pressure wave, asdepicted in FIG. 1 and, therefor, provides a measure of the systolicslope of the blood pressure wave. Obviously, as the systolic slopeincreases, the slope of line 80 decreases, and vice versa. It here willbe noted that in the above-mentioned Weaver et al article, the slope ofthe straight line 80 is determined and utilized in a program fordistinguishing between true Korotkov sounds and artifacts. The maximumand minimum cuff pressures at which true Korotkov sounds are obtainedprovide a measure of the systolic and diastolic blood pressures,respectively, as seen in FIG. 4. The same process disclosed in theWeaver et al article may be used in the present invention to distinguishbetween true Korotkov sounds and artifacts in order that a true measureof the systolic slope may be obtained. It here will be noted thatknowledge of the systolic and diastolic blood pressures is not requiredin the practice of the present invention. Therefore, in the use of theapparatus of FIG. 3, the slope of the line 80 may be established usingonly points adjacent the center of the line 80, and not those adjacentthe opposite ends thereof where the Korotkov sounds are much weaker. Ofcourse, the apparatus may be used for measuring systolic and diastolicblood pressures, and such pressures may be displayed and/or recorded orstored along with the diastolic slope measurements, if desired. Sincethe present invention is not specifically directed to the method ofdistinguishing between true Korotkov sounds and artifacts, it will beunderstood that such artifacts are removed by suitable processing of thesignals from the detector 52, and that points in the plot of FIG. 4 towhich the straight line 80 is fitted are obtained using true Korotkovsounds, not artifacts.

For each cuff deflation a series of points are obtained, as shown inFIG. 4, through which the straight line 80 is fitted. The slope of suchline is readily calculated by the computer. Using the times ofoccurrence of the R-peak waves, the time interval between adjacentR-peak waves is determined, and the reciprocal thereof is calculated toprovide a measure of heart rate during the cuff deflation. During anexercise cycle, or protocol, the above-described operation is repeatedwhereby a plurality of values of slope as a function of heart beatmeasurement, or of time, are obtained, which values may be displayedand/or recorded at display and/or recording unit 74 of FIG. 3. In thepresent application, the the RK interval versus cuff pressure slope(i.e. slope of line 80 of FIG. 4) is referred to as RK slope, forconvenience.

Reference now is made to FIGS. 5A-5D and FIGS. 6A-6D wherein records ofthe type which may be provided by the present system are shown. Inparticular, the slope of the straight line fitted to the measured pointsfor each cuff deflation (i.e. RK slope) as a function of heart rate isplotted. Data for these plots of FIGS. 5A-5B was obtained from fourhealthy subjects having no known CAD while those of FIGS. 6A-6D haveCAD. The symbol X marks the point obtained with the subject at rest,before exercise. Points obtained during exercise are identified by thesymbol □, and those obtained after exercise are identified by the symbolO. Points for the plots were obtained at two-minute intervals, whichintervals may be programmed in the computer 44, or entered through thekeyboard 72. It will be understood that substantially continuousmeasurements may be made, and plotted, there being no requirement forthe two-minute spacing between measurements. A clock 44B, shown in FIG.3, is included to provide time measurements.

From FIGS. 5A-5D, it will be noted that the RK interval/cuff pressureslope (RK slope) for the four healthy subjects at rest, before exercise,is within the range of approximately 0.6 to 1.5. For subjects with knownCAD, the resting slope generally equals or exceeds 2, as seen in FIGS.6A-6C. Since systolic slope is inversely related to the illustratedslope, it will be seen that the resting systolic slope for a subjectwith known CAD is generally equal to or less than 0.5. However, in FIG.6D, the subject with CAD is shown to have a normal starting slope ofapproximately 1.

During exercise, the RK slope for healthy subjects decreasessubstantially exponentially to a value slightly above zero, as shown inFIGS. 5A-5D. Since the RK slope is inversely proportional to thesystolic slope of the blood pressure wave, this indicates that thesystolic slope increases to near-vertical. The undulating nature of theplot of RK slope shown in FIG. 5B during exercise is not typical ofhealthy subjects.

For CAD subjects, the RK slope also generally decreases during exercise,as seen in FIGS. 6A, 6B and 6C but never reaches levels as low as thosereached by healthy subjects. In one CAD case, illustrated in FIG. 6D,there was essentially no change in slope during the entire cycle whichtoo is unlike the change in slope observed in healthy subjects.

After exercise, the RK slope for healthy subjects, shown in FIGS. 5A-5D,slowly returns to the pre-exercise level, while remaining generallywithin the upper and lower limits reached during exercise. For mostsubjects with CAD (FIGS. 6A-6C) the slope rapidly rises during thepost-exercise period. Often, the post-exercise slope exceeds thepre-exercise slope, as seen in FIGS. 6A-6B, which means that thesystolic slope of the brachial artery pulse is low, as is the ejectionfraction EF. As mentioned above, in the one CAD case illustrated in FIG.6D, the post-exercise slope did not significantly change.

Although the operation of the system shown in FIG. 3 for obtaining ameasure of the systolic slope during an exercise cycle is believed to beapparent, a brief description thereof with reference to the flow chartof FIG. 7 now will be provided. Various operations indicated therein areunder control of the computer 44, responsive to programming instructionscontained in memory 44A. Obviously, one or more programming steps may beinvolved in the actual implementation of the indicated operation. Sincethe programming of such steps for the indicated operations is wellwithin the skill of the average programmer, a complete program listingis not required and is not included herein.

With the cuff 30 and transducers 46 and 60 properly secured to thesubject, the test is started as indicated by START step 100, at whichtime system power is turned on or a reset operation is performed, bymeans not shown. Initialization step 102 includes initial setting ofcounters, registers and the like in the computer 44. Informationconcerning the subject, such as the subject's name, may be enteredthrough the keyboard 72 at step 104. At step 106, the stage, or portion,of the exercise cycle to be started by the subject is entered by meansof the keyboard. For example, at the beginning of the test, the word"pre-exercise" may be entered.

With the subject on a treadmill, stationary bicycle, or the like, cuffinflation step 108 is entered wherein the cuff 30 is inflated undercontrol of the computer to a pressure above systolic blood pressurethrough operation of the cuff pressure controller 34 to occlude bloodflow in the brachial artery. Next, at step 110, the cuff pressure isreduced to a pressure at which true Korotkov, or artifact, sounds arefirst detected, which, for true Korotkov sounds, is the systolic bloodpressure. At this point, the cuff pressure is entered into the computermemory 44A through use of transducer 36, amplifier 38, A/D converter 40and digital multiplexer 42, as indicated by step 112.

Next, at step 114, an R-peak wave is detected and its time of arrival isentered in the computer memory. The time of arrival of an associatedKorotkov sound also is entered into the computer memory. As noted above,in addition to the detection of true Korotkov sounds, the K-sounddetector 52 may also respond to artifacts, in which case the time ofarrival of such artifacts also is entered into the computer memory. Forany given R-peak wave the time of arrival of the true K-sound and thatof one or more artifacts may be stored.

At step 116, the RK-interval is calculated, and the RK-interval value,or values, are stored (step 118) with the associated cuff pressure. Thecuff pressure, at step 120, is then reduced an incremental amount of,say 4 mmHg. The decision step 122 next is performed to determine whetheror not outputs are produced from the K-sound detector 52. If not, it isknown that cuff pressure has been reduced beneath diastolic pressure. Ifthe decision is affirmative, i.e. that K-sounds are still beingdetected, step 112 is again entered, whereupon the new reduced cuffpressure value is stored, together with new associated RK-intervalvalues. When cuff pressure is reduced below diastolic pressure at whichtime K-sounds no longer are detected, decision step 122 is negative, andstep 124 is entered whereupon heart rate is calculated using a count ofthe R-peak waves. The heart rate is calculated for the preceeding periodbetween cuff inflation and cuff deflation during which a series ofRK-intervals at declining cuff pressures is obtained. At step 126, trueKorotkov sounds are distinguished from artifacts, and such artifacts aredeleted from further processing. In any system, including the present,in which Korotkov sounds are detected, other sounds also are detected bythe K-sound detector, particularly when the subject is exercising andsuch artifacts must be eliminated from the true Korotkov sounds in orderto obtain an accurate measure of the systolic slope. As noted above,algorithms for discriminating between true Korotkov sounds and artifactsare included in the above-mentioned Weaver et al article.

Using a minimum mean-squared algorithm, a straight line is fitted to theRK intervals obtained from true Korotkov sounds as indicated at step128, and the slope of said line is calculated at step 130. At step 132,using the slope calculated at step 130 and heart rate calculated at step124, a point is recorded on a slope versus heart rate plot (of a typeshown in FIGS. 5A-5D and 6A-6D). The decision step 134 then is enteredat which point a decision is made as to whether or not the test is to becontinued. Keyboard switches, not shown, may be included for manualentry of the decision into the computer 44. If the decision is made tocontinue the test, step 106 is reentered, at which point the operator,or physician, may enter the next stage in the exercise cycle, such as"exercise". The subject then begins, or continues, that portion of theexercise cycle, and another measure of systolic slope is made and addedto the plot. If the test is over, step 136, is entered at which point ananalysis is made of the plot by the physician to determine whether ornot the plot differs from those of healthy subjects for diagnosis ofCAD. The test and diagnosis ends at step 138. It here will be noted thatcertain steps of the flow chart may be performed in different order.

A number of parameters of, or derived from, the plot of the measure ofsystolic slope (here, RK-interval/cuff pressure slope) versus heartrate, time, exercise protocol, or the like, may be used for obtaining avalue indicative of the subject's heart condition. Pertinent parameterswhich may be obtained from a plot of RK-slope versus time, include thefollowing, some of which have been described above:

1. Resting RK Slope, prior to exercise,

2. Rate at which the RK slope decreases during a period of timeimmediately following the start of exercise,

3. Slope of the RK slope versus time plot at the beginning of exercise,

4. Increase in RK slope during exercise,

5. Change in RK slope two minutes after exercise ends,

6. Rate of change in the RK-slope after two minutes after exercise ends,and

7. Highest value of RK slope after exercise.

Typical relative values of the parameters for persons without CAD andpersons with CAD are given in table I below wherein the parameternumbers correspond to those in the above list of parameters.

                  TABLE I                                                         ______________________________________                                        Typical Relative Parameter Values                                                          Subjects W/O  Subjects with                                      Parameter #  CAD           CAD                                                ______________________________________                                        1            Low           High                                               2            Large         Small                                              3            Small         Large                                              4            No Increase   Small Increase                                     5            Decrease      Increase                                           6            Small         Large                                              7            Small         Large                                              ______________________________________                                    

Reference now is made to FIG. 8 wherein a graph, or plot, ofmeasurements of RK slope versus time for a subject without CAD and asubject with CAD are shown, which graph is readily available as anoutput from the computer. Parameters 1 and 3-7 are identified on thegraph of the subject with CAD. It will be noted that the slope of thegraph during the first several minutes of exercise changes substantiallyexponentially for the subject without CAD. On the other hand, the slopeof the graph for the subject with CAD during the same initial timeperiod is substantially constant for approximately two minutes, thenabruptly decreases. This rate of decrease of the slope is employed inthe evaluation of parameter 2.

For each of the parameters, threshold values may be set, or establishedfrom an examination of data from a large number of subjects. Forexample, the threshold for parameter 1, the resting RK-slope prior toexercise, is set between the average for persons with CAD and theaverage for persons without CAD. From an examination of FIGS. 5A through5D for healthy subjects the average resting RK-slope before exercise ison the order of 1.2, and from FIGS. 6A through 6D for subjects withknown CAD, the average resting slope is on the order of 2.5. A thresholdvalue between these averages of, say 1.8 may be employed. This, andthresholds for the other parameters are stored in the computer memory.For parameter 1, the computed resting RK-slope is compared to the 1.8threshold value and, if it is less than the threshold it is considerednormal. If, as a result of the comparison, the parameter is above thethreshold, or cut-point, a value of 1 (one) may be assigned thereto, andif it is below the threshold, a value of -1 may be assigned thereto.These outputs are weighted according to the importance of the parameterin the diagnosis; with negative weights being assigned to parameterswhere necessary. The weighted values for the various parameters simplymay be added to provide an overall figure indicative of the condition ofthe subject's coronary arteries. This figure, together with theindividual weighted values may be read out from the computer. Such asystem is well adapted for screening large numbers of subjects for CAD.

It will be apparent that the parameter values may be obtained directlyfrom the plot or graph of the RK-slope versus time and that manualcalculation may be employed in the evaluation. Alternatively, thecomputer is well adapted for performing such calculations. In FIG. 9, towhich reference now is made, details for the block 136 of the FIG. 7flow chart are shown for computer evaluation of the RK-slope vs timeinformation obtained during an exercise routine of a subject. Parameters1-7 are determined and/or evaluated and weighted at steps 136-1 through136-7, respectively, and at step 136-8 the weighted values are summed,and the results are displayed.

It here will be noted that a nonlinear discriminant function which isnot suitable for manual analysis also may be included in an algorithmfor computer evaluation of measured data.

Of course, the invention is not limited to the above-describedalgorithmic process. For example, the above-described parameters can beweighted to indicate the relative abnormality of the heart condition.These weighted values may be summed and the total compared to acut-point for an indication of a normal or an abnormal condition. Again,such an evaluation may be performed manually or by the computer based onthe data obtained during the exercise routine.

Heart rate can be substituted for time in the above analyses. All of theparameters except parameter 2 are defined as above. For use with theplot involving heart rate, parameter 2 is defined as the constant c whenthe function S(r)=Ke^(-cr) is fit to the RK slope versus heart rate datapoints, where S(r) is the slope, r is the rate, and K is anotherconstant.

The invention having been described in detail in accordance withrequirements of the patent statutes, various other changes andmodifications will suggest themselves to those skilled in the art. Sincethe slope of RK interval as a function of cuff pressure is a function ofsystolic slope, it may be converted to systolic slope which may beplotted as a function of time, heartbeat rate, or the like. Anotherobvious change includes the use of a manually inflatable cuff ratherthan the illustrated arrangement wherein cuff inflation and deflationare under control of the computer. Also, as mentioned above anddescribed in the above-mentioned Weaver et al article, systolic anddiastolic blood pressure measurements may be obtained from cuff pressuremeasurements made when true Korotkov sounds are first heard during acuff deflation, and are last heard, and these pressures also may bedisplayed and/or recorded. As noted above, the operation of the presentapparatus does not depend upon determination of systolic and diastolicblood pressures.

Also, it will be apparent that inputs may be supplied to the computerfrom the exercise device, or the like, used by the subject whereby thework performed by the subject throughout the exercise cycle may berecorded.

Also, it will be apparent that means other than interrupt inputs may beused to input the time of occurance of the R-peak wave and Korotkovsound to the computer. Either a general purpose or dedicated computermay be employed. Also, a recording of the necessary input may be made,and the recording played back to provide the computer inputs.Additionally, it will be apparent that other blood pressure transducersand systems may be used from which a measure of the systolic slope maybe obtained, including, for example, invasive devices. It is intendedthat the above and other such changes and modifications shall fallwithin the spirit and scope of the invention defined in the appendedclaims.

We claim:
 1. Apparatus for use in identifying subjects having coronaryartery disease comprising,an inflatable cuff for encircling a subject'sarm, means for inflating and deflating said cuff through a range ofpressures between systolic pressure and diastolic pressure within whichpressure range Korotkov sounds are produced, pressure transducer meansresponsive to cuff pressure and having an output signal related thereto,electrode means for sensing electrocardiographic signals from thesubject, R-wave peak detector means for detecting the peak of the R-wavein the electrocardiographic signals, transducer means for sensingKorotkov sounds during a cuff deflation, Korotkov sound detecting meansfor detecting Korotkov sounds in the output from said Korotkov soundtransducer means, means responsive to the outputs from said pressuretransducer, R-wave peak detector, and Korotkov sound detector means forproducing a signal representative of the systolic slope of bloodpressure waves during a cuff deflation, means for recurrently operatingsaid means for producing a signal representative of the systolic slopefor obtaining a plurality of said signals representative of systolicslope during different periods of an exercise cycle that includesaerobic exercise performed by the subject, means for detecting andevaluating changes in said signals representative of systolic slopeoccurring during said exercise cycle for identifying subjects havingcoronary artery disease.
 2. Apparatus as defined in claim 1 includingdisplay means, andmeans for displaying said signals representative ofsystolic slope at said display means.
 3. Apparatus for use inidentifying subjects having coronary artery disease comprising,aninflatable cuff for encircling a subject's arm, means for inflating anddeflating said cuff through a range of pressures between systolic anddiastolic pressures within which pressure range Korotkov sounds areproduced, pressure transducer means responsive to cuff pressure andhaving an output signal related thereto, electrode means for sensingelectrocardiographic signals from the subject, R-wave peak detectormeans for detecting the peak of the R-wave in the electrocardiographicsignals, transducer means for sensing Korotkov sounds during a cuffdeflation, Korotkov sound detecting means for detecting Korotkov soundsin the output from said Korotkov sound transducer means, meansresponsive to the outputs from said pressure transducer, R-wave peakdetector, and Korotkov sound detector means for producing a signalrepresentative of the slope of blood pressure waves during a cuffdeflation, means for recurrently operating said means for producing asignal representative of the systolic slope for obtaining a plurality ofsaid signals representative of systolic slope during different periodsof an exercise cycle that includes aerobic exercise performed by thesubject, means for determining heart rate of the subject during theexercise cycle, display means, and means for displaying a plot of saidsignals representative of systolic slope versus heart rate of thesubject at said display means.
 4. Apparatus as defined in claim 2wherein the display provided by said display means includes a plot ofsaid signals representative of systolic slope versus time.
 5. Apparatusfor use in identifying subjects having coronary artery diseasecomprising,an inflatable cuff for encircling a subject's arm, means forinflating and deflating said cuff through a range of pressures betweensystolic and diastolic pressures within which pressure range Korotkovsounds are produced, pressure transducer means responsive to cuffpressure and having an output signal related thereto, electrode meansfor sensing electrocardiographic signals from the subject, R-wave peakdetector means for detecting the peak of the R-wave in theelectrocardiographic signals, transducer means for sensing Korotkovsounds during a cuff deflation, Korotkov sound detecting means fordetecting Korotkov sounds in the output from said Korotkov soundtransducer means, means responsive to the outputs from said pressuretransducer, R-wave peak detector, and Korotkov sound detector means forproducing a signal representative of the slope of blood pressure wavesduring a cuff deflation, means for recurrently operating said means forproducing a signal representative of the systolic slope for obtaining aplurality of said signals representative of systolic slope duringdifferent periods of an exercise cycle that includes aerobic exerciseperformed by the subject, means for detecting and evaluating changes insaid signals representative of systolic slope occurring during saidexercise cycle for identifying subjects having coronary artery disease,said means for producing a signal representative of the systolic slopeof blood pressure wave including, means for accumulating a plurality ofcuff pressure values and associated RK intervals comprising the timebetween the occurrence of an output from the R-wave peak detector meansand the associated Korotkov sound signal from said Korotkov sounddetecting means, and means for fitting a straight line to said RKintervals and associated cuff pressure values obtained during a cuffdeflation, the slope of which straight line is inversely proportional tothe systolic slope of the blood pressure wave.
 6. Apparatus as definedin claim 5 including display means,means for determining heart rate ofthe subject during the exercise cycle, and means for displaying a plotof the slope of said straight line versus heart rate at said displaymeans.
 7. Apparatus as defined in claim 1 wherein a systolic slope whichincreases then decreases during aerobic exercise is evaluated by saidevaluating means as being indicative of coronary artery disease in thesubject.
 8. Apparatus as defined in claim 1 wherein a systolic slopeafter aerobic exercise which is less than the pre-exercise systolicslope is evaluated by said evaluating means as being indicative ofcoronary artery disease in the subject.
 9. Apparatus as defined in claim1 wherein a rate of change of systolic slope approximately two minutesafter aerobic exercise is terminated which is greater than that forindividuals without coronary artery disease is evaluated by saidevaluating means as being indicative of coronary artery disease in thesubject.
 10. Apparatus as defined in claim 1 wherein a rate of change ofsystolic slope during a period of time immediately following the startof aerobic exercise that is less than that for individuals withoutcoronary artery disease is evaluated by said evaluating means as beingindicative of coronary artery disease.
 11. Apparatus as defined in claim1 wherein a systolic slope during the initial portion of the aerobicexercise segment of the exercise cycle is less than that for individualswithout coronary artery disease is evaluated by said evaluating means asbeing indicative of coronary artery disease in the subject. 12.Apparatus as defined in claim 1 wherein a systolic slope after aerobicexercise which is less than that for individuals without coronary arterydisease is evaluated by said evaluating means as being indicative ofcoronary artery disease.
 13. A method of screening subjects for coronaryartery disease comprising,obtaining a measure of the systolic slope ofan artery blood pressure wave of a subject by use of an inflatable cuffwith a transducer responsive to cuff pressure, R-wave detecting means,and Korotkov sound detecting means from which transducer and detectingmeans blood pressure, R-wave and Korotkov sound signals are obtained,respectively, said step of obtaining a measure of the systolic slopeincluding recurrently processing said signals to obtain a signal relatedto the slope of a straight line fitted to R-wave Korotkov soundintervals versus cuff pressure during cuff deflation between systolicand diastolic blood pressures, which slope related signal provides ameasure of systolic slope during said cuff deflation, repeating saidstep of obtaining a measure of the systolic slope for obtaining aplurality of said measurements over a period of time during which thesubject executes an exercise protocol which includes rest before aerobicexercise, aerobic exercise, and rest after aerobic exercise, providing aplot of said measurements, evaluating said plot on the basis of aplurality of different parameters, weighting values obtained from saidevaluations, summing the weighted values to obtain a sum, anddetermining if said sum is outside a predetermined cut-point, a sumoutside a predetermined cut-point being used to identify subjects withcoronary artery disease.
 14. A method as defined in claim 13 wherein themeasurement of slope obtained while the subject is at rest prior toexercise comprises one of said plurality of different parameters whichis evaluated to obtain a value for weighting.
 15. A method as defined inclaim 13 wherein said plurality of parameters includes detecting therate of change of slope measurements during the beginning of theexercise protocol.
 16. A method as defined in claim 13 wherein saidplurality of parameters includes detecting the slope of said plot at thebeginning of the exercise protocol.
 17. A method as defined in claim 13wherein said plurality of parameters includes detecting a change indirection of the measurement of slope during the exercise protocol. 18.A method as defined in claim 13 wherein said plurality of parametersincludes detecting the amount of change in the slope measurements duringa period of time after exercise during the exercise protocol.
 19. Amethod as defined in claim 13 wherein said plurality of parametersincludes detecting the rate of change in the slope measurement occurringduring a period of time after exercise during the exercise protocol. 20.A method as defined in claim 13 wherein said plurality of parametersincludes detecting the highest value of measurement of slope occurringafter exercise during the exercise protocol.
 21. Apparatus for use inidentifying subjects having coronary artery disease comprising,means forobtaining measurements of the systolic slope of an arterial bloodpressure wave of the subject during different periods of an exercisecycle which includes pre-exercise rest, aerobic exercise on a treadmill,stationary bicycle, or the like, and post-exercise rest portions, meansresponsive to said means for obtaining measurements of the systolicslope for evaluating changes in slope occurring during said exercisecycle for identifying subjects having coronary artery disease. 22.Apparatus as defined in claim 21 wherein a systolic slope whichincreases then decreases during aerobic exercise is evaluated by saidevaluating means as being indicative of coronary artery disease in thesubject.
 23. Apparatus as defined in claim 21 wherein a systolic slopeafter aerobic exercise which is less than the pre-exercise systolicslope is evaluated by said evaluating means as being indicative ofcoronary artery disease in the subject.
 24. Apparatus as defined inclaim 21 wherein a rate of change of systolic slope approximately twominutes after aerobic exercise is terminated which is greater than thatfor individuals without coronary artery disease is evaluated by saidevaluating means as being indicative of coronary artery disease in thesubject.
 25. Apparatus as defined in claim 21 wherein a rate of changeof systolic slope during a period of time immediately following thestart of aerobic exercise that is less than that for individuals withoutcoronary artery disease is evaluated by said evaluating means as beingindicative of coronary artery disease.
 26. Apparatus as defined in claim21 wherein a systolic slope during the initial portion of the aerobicexercise segment of the exercise cycle is less than that for individualswithout coronary artery disease is evaluated by said evaluating means asbeing indicative of coronary artery disease in the subject. 27.Apparatus as defined in claim 21 wherein a systolic slope after aerobicexercise which is less than that for individuals without coronary arterydisease is evaluated by said evaluating means a being indicative ofcoronary artery disease.